Takashi Higuchi, S. Oka, H. Furukawa, K. Shimada, S. Tohma
{"title":"Lack of Association of rs12702634 in RPA3-UMAD1 With Interstitial Lung Diseases in Japanese Rheumatoid Arthritis Patients","authors":"Takashi Higuchi, S. Oka, H. Furukawa, K. Shimada, S. Tohma","doi":"10.1177/11772719221091758","DOIUrl":"https://doi.org/10.1177/11772719221091758","url":null,"abstract":"Background: Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in RPA3-UMAD1. We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association. Methods: Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease. Results: No association was detected for rs12702634 with ILD in RA (P = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association (P = .0996, OR 1.52, 95% CI 0.92–2.49). Conclusions: The present study demonstrated no association of RPA3-UMAD1 rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47610435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. A. Puchenkova, V. Soldatov, Andrei E. Belykh, O. Bushueva, G. Piavchenko, Artem A Venediktov, N. Shakhpazyan, A. Deykin, M. Korokin, M. Pokrovskiy
{"title":"Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application","authors":"O. A. Puchenkova, V. Soldatov, Andrei E. Belykh, O. Bushueva, G. Piavchenko, Artem A Venediktov, N. Shakhpazyan, A. Deykin, M. Korokin, M. Pokrovskiy","doi":"10.1177/11772719221095676","DOIUrl":"https://doi.org/10.1177/11772719221095676","url":null,"abstract":"Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokines. Previous studies emphasize an altered expression and a changed epigenetic regulation of key cytokines in AAA tissue samples. Such cytokines as IL-6, IL-10, IL-12, IL-17, IL-33, IL-1β, TGF-β, TNF-α, IFN-γ, and CXCL10 seem to be crucial in AAA pathogenesis. Some data obtained in animal studies show a protective function of IL-10, IL-33, and canonical TGF-β signaling, as well as a dual role of IL-4, IFN-γ and CXCL10, while TNF-α, IL-1β, IL-6, IL-12/IL-23, IL-17, CCR2, CXCR2, CXCR4 and the TGF-β noncanonical pathway are believed to aggravate the disease. Altogether data highlight significance of cytokines as informative markers and predictors of AAA. Pathologic serum/plasma concentrations of IL-1β, IL-2, IL-6, TNF-α, IL-10, IL-8, IL-17, IFN-γ, and PDGF have been already found in AAA patients. Some of the changes correlate with the size of aneurysms. Moreover, the risk of AAA is associated with polymorphic variants of genes encoding cytokines and their receptors: CCR2 (rs1799864), CCR5 (Delta-32), IL6 (rs1800796 and rs1800795), IL6R (rs12133641), IL10 (rs1800896), TGFB1 (rs1800469), TGFBR1 (rs1626340), TGFBR2 (rs1036095, rs4522809, rs1078985), and TNFA (rs1800629). Finally, 5 single-nucleotide polymorphisms in gene coding latent TGF-β-binding protein (LTBP4) and an allelic variant of TGFB3 are related to a significantly slower AAA annual growth rate.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49488601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Purpose, Partnership, and Possibilities: The Implementation of the Dog Aging Project Biobank.","authors":"Lara Mouttham, Marta G Castelhano","doi":"10.1177/11772719221137217","DOIUrl":"https://doi.org/10.1177/11772719221137217","url":null,"abstract":"<p><strong>Background: </strong>Biobanks have been supporting longitudinal prospective and retrospective studies by providing standardized services for the acquisition, transport, processing, storage, and distribution of high-quality biological material and associated data. Here, we describe how the Dog Aging Project (DAP), a large-scale longitudinal study of the domestic dog (<i>Canis familiaris</i>) with translational applications for humans, developed a biobank of canine biospecimens and associated data.</p><p><strong>Design and methods: </strong>This was accomplished by working with the Cornell Veterinary Biobank, the first biobank in the world to receive accreditation to ISO 20387:2018-General Requirements for Biobanking. The biobank research team was involved in the early collection stages of the DAP, contributing to the development of appropriate workflows and processing fit-for-purpose biospecimens. In support of a dynamic strategy for real-time adjustment of processes, a pilot phase was implemented to develop, test, and optimize the biospecimen workflows, followed by an early phase of collection, processing, and banking of specimens from DAP participants.</p><p><strong>Results: </strong>During the pilot and early phases of collection, the DAP Biobank stored 164 aliquots of whole blood, 273 aliquots of peripheral blood mononuclear cells, 130 aliquots of plasma, and 70 aliquots of serum, and extracted high molecular weight genomic DNA suitable for whole-genome sequencing from 109 whole blood specimens. These specimens, along with their associated preanalytical data, have been made available for distribution to researchers.</p><p><strong>Conclusion: </strong>We discuss the challenges and opportunities encountered during the implementation of the DAP Biobank, along with novel strategies for promoting biobanking sustainability such as partnering with a DAP quality assurance manager and a DAP marketing and communication specialist and developing a pilot grant structure to fund small innovative research projects.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"17 ","pages":"11772719221137217"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/fb/10.1177_11772719221137217.PMC9716607.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9635853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paweł Krzemień, Sławomir Kasperczyk, Maciej Banach, Aleksandra Kasperczyk, Michał Dobrakowski, Tomasz Tomasik, Adam Windak, Mirosław Mastej, Alberico Catapano, Kausik K Ray, Dimitri P Mikhailidis, Peter P Toth, George Howard, Gregory Yh Lip, Maciej Tomaszewski, Fadi J Charchar, Naveed Sattar, Bryan Williams, Thomas M MacDonald, Peter E Penson, Jacek J Jóźwiak
{"title":"Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress.","authors":"Paweł Krzemień, Sławomir Kasperczyk, Maciej Banach, Aleksandra Kasperczyk, Michał Dobrakowski, Tomasz Tomasik, Adam Windak, Mirosław Mastej, Alberico Catapano, Kausik K Ray, Dimitri P Mikhailidis, Peter P Toth, George Howard, Gregory Yh Lip, Maciej Tomaszewski, Fadi J Charchar, Naveed Sattar, Bryan Williams, Thomas M MacDonald, Peter E Penson, Jacek J Jóźwiak","doi":"10.1177/11772719211066791","DOIUrl":"https://doi.org/10.1177/11772719211066791","url":null,"abstract":"Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P = .038) and 11% lower concentration of UA (P = .005). TOS was 20% lower (P = .014). The activity of SOD was up to 5% higher (P = .037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"17 ","pages":"11772719211066791"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/ff/10.1177_11772719211066791.PMC8808033.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rita K Upmacis, Wendy L Becker, Donna M Rattendi, Raven S Bell, Kelsey D Jordan, Shayan Saniei, Elena Mejia
{"title":"Analysis of Sex-Specific Prostanoid Production Using a Mouse Model of Selective Cyclooxygenase-2 Inhibition.","authors":"Rita K Upmacis, Wendy L Becker, Donna M Rattendi, Raven S Bell, Kelsey D Jordan, Shayan Saniei, Elena Mejia","doi":"10.1177/11772719221142151","DOIUrl":"https://doi.org/10.1177/11772719221142151","url":null,"abstract":"<p><strong>Background: </strong>Prostanoids are a family of lipid mediators formed from arachidonic acid by cyclooxygenase enzymes and serve as biomarkers of vascular function. Prostanoid production may be different in males and females indicating that different therapeutic approaches may be required during disease.</p><p><strong>Objectives: </strong>We examined sex-dependent differences in COX-related metabolites in genetically modified mice that produce a cyclooxygenase-2 (COX2) enzyme containing a tyrosine 385 to phenylalanine (Y385F) mutation. This mutation renders the COX2 enzyme unable to form a key intermediate radical required for complete arachidonic acid metabolism and provides a model of selective COX2 inhibition.</p><p><strong>Design and methods: </strong>Mice heterozygous for the Y385F mutation in COX2 were mated to produce cohorts of wild-type, heterozygous, and COX2 mutant mice. We investigated whether the genotype distribution followed Mendelian genetics and studied whether sex-specific differences could be found in certain prostanoid levels measured in peritoneal macrophages and in urinary samples.</p><p><strong>Results: </strong>The inheritance of the COX2 mutation displayed a significant deviation with respect to Mendel's laws of genetics, with a lower-than-expected progeny of weaned COX2 mutant pups. In macrophages, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) production following lipopolysaccharide (LPS) and interferon gamma (IFNγ) stimulation was COX2-dependent in both males and females, and data indicated that crosstalk between the nitric oxide (NO) and COX2 pathways may be sex specific. We observed significant differences in urinary PGE<sub>2</sub> production by male and female COX2 mutant mice, with the loss of COX2 activity in male mice decreasing their ability to produce urinary PGE<sub>2</sub>. Finally, female mice across all 3 genotypes produced similar levels of urinary thromboxane (measured as 11-dehydro TxB<sub>2</sub>) at significantly higher levels than males, indicating a sex-related difference that is likely COX1-derived.</p><p><strong>Conclusions: </strong>Our findings clearly demonstrate that sex-related differences in COX-derived metabolites can be observed, and that other pathways (such as the NO pathway) are affected.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"17 ","pages":"11772719221142151"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/a0/10.1177_11772719221142151.PMC9749041.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aberrant expression of miR-138 as a novel diagnostic biomarker in systemic sclerosis.","authors":"Paria Bayati, Hadi Poormoghim, Nazanin Mojtabavi","doi":"10.1177/11772719221135442","DOIUrl":"https://doi.org/10.1177/11772719221135442","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs are short nucleotide sequences that contribute to the regulation of various biological functions and therefore their roles have been investigated in many pathologic conditions such as epithelial to mesenchymal transition in cancer and fibrosis; among them, miR-138 has been mostly studied in cancer biology and is well-known for its suppressing effect on cancer progression. Being able to suppress major pathways involved in EMT, miR-138 could be a good candidate to be investigated in fibrotic responses too. Based on our previous studies, and the capability of miR-138 to target and regulate several components of the EMT pathway; we hypothesized a role for miR-138 in systemic sclerosis. Accordingly, the gene expression of miR-138 was assessed to find any alterations in the whole blood of the SSc patients.</p><p><strong>Methods: </strong>Blood was collected from 70 patients with systemic sclerosis (equally divided between 2 groups of limited and diffuse categories) and 30 healthy individuals as controls. RNA was immediately isolated from the fresh whole blood; afterward, the resulting RNA was reverse transcribed into cDNA and then the relative expression of miR-138 was compared between the patients and the controls by the means of qPCR, and specific TaqMan primer and probes.</p><p><strong>Results: </strong>The relative expression of miR-138 was significantly lower in patients with systemic sclerosis compared to the controls. No significant difference was observed between the limited and diffuse patient groups. ROC curve analysis showed an appropriate diagnostic value of miR-138 in effectively differentiating SSc patients from the healthy controls.</p><p><strong>Conclusion: </strong>miR-138 is likely involved in the pathogenesis of SSc and with further evaluations may be utilized as a diagnostic biomarker in SSc. Also, targeting miR-138 in future studies could be promising for finding a novel treatment option for patients with SSc.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"17 ","pages":"11772719221135442"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/8e/10.1177_11772719221135442.PMC9742580.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10731064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Siljan, D. Sivakumaran, C. Ritz, S. Jenum, T. Ottenhoff, E. Ulvestad, J. Holter, L. Heggelund, H. Grewal
{"title":"Host Transcriptional Signatures Predict Etiology in Community-Acquired Pneumonia: Potential Antibiotic Stewardship Tools","authors":"W. Siljan, D. Sivakumaran, C. Ritz, S. Jenum, T. Ottenhoff, E. Ulvestad, J. Holter, L. Heggelund, H. Grewal","doi":"10.1177/11772719221099130","DOIUrl":"https://doi.org/10.1177/11772719221099130","url":null,"abstract":"Background: Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for differentiating between viral and bacterial CAP, unnecessary antibacterial therapy could be avoided in viral CAP patients. Methods: In 156 adults hospitalized with CAP classified to have bacterial, viral, or mixed viral-bacterial infection based on microbiological testing or both microbiological testing and procalcitonin (PCT) levels, we aimed to identify discriminatory host transcriptional signatures in peripheral blood samples acquired at hospital admission, by applying Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA). Results: In patients classified by microbiological testing, a 9-transcript signature showed high accuracy for discriminating bacterial from viral CAP (AUC 0.91, 95% CI 0.85-0.96), while a 10-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.91, 95% CI 0.86-0.96). In patients classified by both microbiological testing and PCT levels, a 13-transcript signature showed excellent accuracy for discriminating bacterial from viral CAP (AUC 1.00, 95% CI 1.00-1.00), while a 7-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.93, 95% CI 0.87-0.98). Conclusion: Our findings support host transcriptional signatures in peripheral blood samples as a potential tool for guiding clinical decision-making and antibiotic stewardship in CAP.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46684929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camille C Gunderson, Rangasudhagar Radhakrishnan, Rohini Gomathinayagam, Sanam Husain, Sheeja Aravindan, Kathleen M Moore, Danny N Dhanasekaran, Muralidharan Jayaraman
{"title":"Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis.","authors":"Camille C Gunderson, Rangasudhagar Radhakrishnan, Rohini Gomathinayagam, Sanam Husain, Sheeja Aravindan, Kathleen M Moore, Danny N Dhanasekaran, Muralidharan Jayaraman","doi":"10.1177/11772719221088404","DOIUrl":"https://doi.org/10.1177/11772719221088404","url":null,"abstract":"<p><p>Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 \"poor\" (<6 months progression free interval [PFI]) and 22 \"favorable\" (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"17 ","pages":"11772719221088404"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/30/10.1177_11772719221088404.PMC8966103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10677071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Shultz, Caroline J Taylor, Riemke Aggio-Bruce, W. T. O'Brien, Mujun Sun, Adrian V Cioanca, George A. Neocleous, Georgia F Symons, R. Brady, A. Hardikar, M. Joglekar, Daniel M Costello, T. O’Brien, R. Natoli, S. McDonald
{"title":"Decrease in Plasma miR-27a and miR-221 After Concussion in Australian Football Players","authors":"S. Shultz, Caroline J Taylor, Riemke Aggio-Bruce, W. T. O'Brien, Mujun Sun, Adrian V Cioanca, George A. Neocleous, Georgia F Symons, R. Brady, A. Hardikar, M. Joglekar, Daniel M Costello, T. O’Brien, R. Natoli, S. McDonald","doi":"10.1177/11772719221081318","DOIUrl":"https://doi.org/10.1177/11772719221081318","url":null,"abstract":"Introduction: Sports-related concussion (SRC) is a common form of brain injury that lacks reliable methods to guide clinical decisions. MicroRNAs (miRNAs) can influence biological processes involved in SRC, and measurement of miRNAs in biological fluids may provide objective diagnostic and return to play/recovery biomarkers. Therefore, this prospective study investigated the temporal profile of circulating miRNA levels in concussed male and female athletes. Methods: Pre-season baseline blood samples were collected from amateur Australian rules football players (82 males, 45 females). Of these, 20 males and 8 females sustained an SRC during the subsequent season and underwent blood sampling at 2-, 6- and 13-days post-injury. A miRNA discovery Open Array was conducted on plasma to assess the expression of 754 known/validated miRNAs. miRNA target identified were further investigated with quantitative real-time PCR (qRT-PCR) in a validation study. Data pertaining to SRC symptoms, demographics, sporting history, education history and concussion history were also collected. Results: Discovery analysis identified 18 candidate miRNA. The consequent validation study found that plasma miR-221-3p levels were decreased at 6d and 13d, and that miR-27a-3p levels were decreased at 6d, when compared to baseline. Moreover, miR-27a and miR-221-3p levels were inversely correlated with SRC symptom severity. Conclusion: Circulating levels of miR-27a-3p and miR-221-3p were decreased in the sub-acute stages after SRC, and were inversely correlated with SRC symptom severity. Although further studies are required, these analyses have identified miRNA biomarker candidates of SRC severity and recovery that may one day assist in its clinical management.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46526443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomarker InsightsPub Date : 2021-10-26eCollection Date: 2021-01-01DOI: 10.1177/11772719211053449
Ker Rui Wong, William T O'Brien, Mujun Sun, Glenn Yamakawa, Terence J O'Brien, Richelle Mychasiuk, Sandy R Shultz, Stuart J McDonald, Rhys D Brady
{"title":"Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury.","authors":"Ker Rui Wong, William T O'Brien, Mujun Sun, Glenn Yamakawa, Terence J O'Brien, Richelle Mychasiuk, Sandy R Shultz, Stuart J McDonald, Rhys D Brady","doi":"10.1177/11772719211053449","DOIUrl":"https://doi.org/10.1177/11772719211053449","url":null,"abstract":"<p><strong>Introduction: </strong>Serum neurofilament light (NfL) is an emerging biomarker of traumatic brain injury (TBI). However, the effect of peripheral injuries such as long bone fracture and skeletal muscle injury on serum NfL levels is unknown. Therefore, the aim of this study was to determine whether serum NfL levels can be used as a biomarker of TBI in the presence of concomitant peripheral injuries.</p><p><strong>Methods: </strong>Rats were randomly assigned to one of four injury groups: polytrauma (muscle crush + fracture + TBI; n = 11); peripheral injuries (muscle crush + fracture + sham-TBI; n = 12); TBI-only (sham-muscle crush + sham-fracture + TBI; n = 13); and triple-sham (n = 7). At 2-days post-injury, serum levels of NfL were quantified using a Simoa HD-X Analyzer.</p><p><strong>Results: </strong>Compared to triple-sham rats, serum NfL concentrations were higher in rats with peripheral injuries-only, TBI-only, and polytrauma. When compared to peripheral injury-only rats, serum NfL levels were higher in TBI-only and polytrauma rats. No differences were found between TBI-only and polytrauma rats.</p><p><strong>Conclusion: </strong>Serum NfL levels did not differ between TBI-only and polytrauma rats, indicating that significant peripheral injuries did not affect the sensitivity and specificity of serum NfL as a biomarker of moderate TBI. However, the finding of elevated serum NfL levels in rats with peripheral injuries in the absence of a TBI suggests that the presence of such injuries may limit the utility of NfL as a biomarker of less severe TBI (eg, concussion).</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211053449"},"PeriodicalIF":3.8,"publicationDate":"2021-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/d9/10.1177_11772719211053449.PMC8554541.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39831627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}